Increasing clinical and experimental data provide evidence that aging and physical frailty are strongly linked[unreadable] to fundamental mechanisms of inflammation. The fundamental hypothesis of RC-4 is that common biological[unreadable] mechanisms in aging may be accelerated in selected disability conditions, such as stroke and hip fracture.[unreadable] The mission of RC-4 is to investigate biologic mechanisms that underlie the disability of advancing age at the[unreadable] tissue, cellular, molecular, and genetic level with a focus on muscle, adipocytes, and endothelial cells. RC-4[unreadable] will provide consultative expertise, technical support and training, and access to services and resources for[unreadable] the conduct of muscle, adipocyte, and vascular biology research in disabled older people. RC-4 will a)[unreadable] investigate inflammatory-oxidative injury markers are the tissue, cellular and genetic level in muscle, adipose[unreadable] tissue and vascular endothelial cells; b) compare the similarities and differences between aging and select[unreadable] disability conditions in terms of sarcopenia, altered muscle structure/function, insulin resistance, and the[unreadable] genetic underpinnings of accelerated atherosclerosis, and c) determine the effects of targeted exercise[unreadable] programs on structural, inflammatory and metabolic abnormalities of muscle, adipose tissue, thrombosis and[unreadable] hemostasis, and vascular endothelium in these disabled populations. RC-4 will collaborate with RC-1 in the[unreadable] design of collaborative translational bench research studies, with RC-2 for measures of muscle performance[unreadable] to understand the clinical relevance of muscle structural and functional abnormalities, with RC-3 to relate[unreadable] abnormalities in body composition and glucose metabolism with changes at the level of muscle and adipose[unreadable] tissue, and with RC-3 to relate systemic measures of inflammation and abnormal metabolism to defects in[unreadable] vasomotor reactivity with abnormalities of thrombosis and markers of endothelial cell injury, and finally with[unreadable] RC-5 to explore statistical relationships of the RC-4 data at the level of tissue, cell, and gene in relation to[unreadable] measures from the other Cores. RC-4 will facilitate Intra- and Inter-Pepper collaborative research. With a[unreadable] better understanding of these structural, molecular, and metabolic muscle abnormalities and their response[unreadable] to exercise, we can optimize exercise interventions that improve muscle structure and functional outcomes,[unreadable] metabolic function, cardiovascular disease risk profile, and consequent risk of arteriosclerosis and[unreadable] thrombosis in these chronic disability conditions.